Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats / A serotonina endógena e exógena, mas não o sumatriptano, melhora as convulsões e a neuroinflamação no modelo de convulsão induzida por pentilenotetrazol em ratos

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

RESUMO Antecedentes: A epilepsia apresenta comorbidades neuropsiquiátricas como depressão, transtorno bipolar e ansiedade. Os medicamentos que visam o tratamento da epilepsia podem ser úteis para a epilepsia e suas comorbidades neuropsiquiátricas. Objetivo: Investigar os efeitos da modulação serotonérgica em citocinas pró-inflamatórias e as convulsões no modelo de convulsão induzida por pentilenotetrazol (PTZ) em ratos. Métodos: Ratos Wistar machos foram injetados intraperitonealmente com serotonina, inibidor seletivo da recaptação da serotonina fluoxetina, sumatriptano agonista do receptor 5-HT1B / D ou solução salina 30 min antes do tratamento com PTZ. As crises comportamentais foram avaliadas pela escala de Racine. As concentrações de IL-1β, IL-6 e TNF-α no soro e tecido cerebral foram determinadas por ELISA. Resultados: A serotonina e a fluoxetina, mas não o sumatriptano, aliviaram as convulsões induzidas por PTZ ao prolongar os tempos de início das convulsões mioclônicas e tônico-clônicas generalizadas. O efeito anticonvulsivo da fluoxetina foi maior do que o da serotonina. Da mesma forma, a serotonina e a fluoxetina, mas não o sumatriptano, reduziram os aumentos induzidos por PTZ nos níveis de IL-1β e IL-6 no soro e no tecido cerebral. Nenhum dos medicamentos administrados, incluindo PTZ, alterou as concentrações de TNF-α. Conclusões: Nossos achados sugerem que a serotonina endógena e exógena exibe efeitos anticonvulsivantes por suprimir a neuroinflamação. Aparentemente, os receptores 5-HT1B / D não medeiam os efeitos anticonvulsivantes e anti-neuroinflamatórios da serotonina.

La depresión: un desafío en la práctica médica general / La depresión: un desafío en la práctica médica general

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)

Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)

Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats

This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg-1·day-1; and oral KXS at a dose of 676 mg·kg-1·day-1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, TGF-β, and TNF-α) levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg-1·day-1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg-1·day-1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.

QT longo desmascarado pela flouxetina / Long QT unmasked by fluoxetine

A síndrome do QT longo induzida por fármacos é uma condição potencialmente fatal, capaz decausar morte súbita como primeira manifestação clínica. Relatamos o caso de paciente jovem que evoluiu comparada cardiorrespiratória em fibrilação ventricular durante internação hospitalar, 24 horas após nefrolitotripsiaextracorpórea. Durante a avaliação foi observado intervalo QT corrigido aumentado de 580 ms e uso de fórmulapara emagrecer que continha fluoxetina 30 mg. Após suspensão da medicação houve normalização do QT,optando-se pelo uso de cardiodesfibrilador implantável pelo alto risco de recorrência da fibrilação ventricular.A síndrome do QT longo pode se manifestar após o uso de fármacos para o tratamento de outras afecções,ressaltando a importância da anamnese rigorosa em busca de antecedentes de morte súbita, assim como darealização de eletrocardiografia antes da introdução de fármacos específicos, de forma a identificar possíveis casosassintomáticos de síndrome do QT longo.

Drug-induced long QT syndrome is a potentially fatal condition that can cause sudden death as a firstclinical manifestation. We report the case of a young patient evolved with cardiorespiratory arrest in ventricularfibrillation during hospitalization, 24 hours after extracorporeal nephrolithotripsy. The patient had an increasedcorrected QT interval of 580 ms and was on weight loss medication containing fluoxetine 30 mg. The QT intervalnormalized after withdrawal of the medication and we chose to use an implantable cardioverter defibrillator dueto the high risk of reoccurrence of ventricular fibrillation. Long QT syndrome may manifest after drug therapyfor other diseases, highlighting the importance of obtaining a through family history of sudden death as well asan ECG before using specific drugs, to identify possible asymptomatic cases of long QT syndrome.

Treatment of depression in older adults beyond fluoxetine / Tratamento de depressão no idoso além do cloridrato de fluoxetina

This review aimed to discuss the importance of the comprehensive treatment of depression among older adults in Brazil. The abuse of selective serotonin reuptake inhibitors, including fluoxetine hydrochloride, as antidepressants has been considered a serious public health problem, particularly among older adults. Despite the consensus on the need for a comprehensive treatment of depression in this population, Brazil is still unprepared. The interface between pharmacotherapy and psychotherapy is limited due to the lack of healthcare services, specialized professionals, and effective healthcare planning. Fluoxetine has been used among older adults as an all-purpose drug for the treatment of depressive disorders because of psychosocial adversities, lack of social support, and limited access to adequate healthcare services for the treatment of this disorder. Preparing health professionals is a sine qua non for the reversal of the age pyramid, but this is not happening yet.

Esse comentário tem como objetivo discutir a importância da multidisciplinariedade do tratamento da depressão do idoso no Brasil. O abuso de prescrições de antidepressivos inibidores seletivos da receptação de serotonina, como o cloridrato de fluoxetina, já tem sido apontado como grave problema de saúde pública, especialmente entre idosos. Embora seja consenso a necessidade de multidisciplinariedade no tratamento da depressão nessa população, o Brasil ainda encontra-se despreparado. A interface entre farmacoterapia e psicoterapia encontra-se prejudicada por falta de serviços, de profissionais especializados e de planejamento assistencial efetivo. A fluoxetina tornou-se uma “muleta” para a cura de males causados pelas adversidades psicossociais, falta de suporte social e de acesso a serviços de saúde adequados para o tratamento desse transtorno em idosos. É condição sine qua non haver preparo para a inversão das pirâmides etárias, o que parece não acontecer atualmente.

Effects of long-term fluoxetine treatment on adrenergic plasticity in rat vas deferens

Chronic antidepressant administration increases neurotrophin levels in the central and peripheral nervous system, leading to an increase of neuronal sprouting, reestablishment of neural networks and neurotransmitter levels. Injured peripheral nerves regenerate at very slow rates. However, the recovery of the hypogastric nerve in rodents after injury is significantly improved with neurotrophin administration. Accordingly, our goal was to determine whether treatment with the antidepressant fluoxetine affects catecholamine levels and neuronal function, after surgical denervation of the rat vas deferens. Noradrenaline levels in the denervated vas deferens were higher in fluoxetine-treated animals than in the vehicle-treated group, as measured by high performance liquid chromatography. In functional studies of smooth muscle contraction, the responses induced by phenylephrine or ATP, as well as pre-synaptic α2-adrenoceptor reactivity, were not modified by chronic treatment with the antidepressant. However, the contraction mediated by neuronal release of noradrenaline induced by tyramine was increased on days 7 and 21 after denervation in rats treated with fluoxetine. These data indicate that fluoxetine can improve functional recovery after rat vas deferens denervation.

A administração crônica de antidepressivos aumenta os níveis de neurotrofinas no sistema nervoso central, levando a um aumento da arborização neuronal, restabelecendo a rede neural e os níveis de neurotransmissores. Lesões do sistema nervoso periférico mostram uma regeneração muito lenta. Entretanto, a recuperação após a lesão do nervo hipogástrico em roedores é significativamente melhorada após a administração de neurotrofinas. Nesse sentido, nosso objetivo foi verificar se o tratamento com o antidepressivo, fluoxetina, interfere nos níveis de catecolaminas e na função neuronal, após a desnervação cirúrgica do ducto deferente de rato. Nos vasos deferentes desnervados, os níveis de catecolaminas nos grupos tratados com fluoxetina foram maiores que no grupo veículo, quantificados em cromatografia líquida de alta eficiência (CLAE). Nos estudos funcionais, a contração da musculatura lisa induzida pela fenilefrina ou pelo ATP, assim como a reatividade pré-sináptica α2-adrenérgica, não foram modificadas com o tratamento crônico de fluoxetina. Contudo, nas contrações mediadas pela liberação neuronal de norepinefrina induzida por tiramina, observou-se aumento da contração nos dias 7 e 21 após a desnevação em ratos tratados com fluoxetina. Esses dados indicam que a fluoxetina pode melhorar a recuperação funcional do vaso deferente de rato após a desnervação.

Morphological aspects of dentin-pulp complex development in the offspring of rats treated with fluoxetine during pregnancy

Aim: To evaluate the morphological aspects of coronal dentinogenesis in the first molars of 1- and 5-day-old rats whose mothers were treated with fluoxetine hydrochloride during pregnancy. Methods: Twelve pregnant Wistar rats were divided randomly into three groups: group C (control), group FL (fluoxetine administered at 10 mg/kg bodyweight), and group FX (fluoxetine administered at 20 mg/kg bodyweight). Saline (0.9%) solution or fluoxetine hydrochloride was administered subcutaneously for the first 21 days of pregnancy. Subsequently, the offspring of these animals was subdivided into subgroups according to age of tooth germ development to be studied: 1 and 5 days of life. C1 and C5 (control group 1 and 5 days of age); FL1 and FL5 (groups treated with 10 mg/kg fluoxetine at 1 and 5 days of age); FX5 and FX1 (groups treated with 20 mg/ kg fluoxetine at 1 and 5 days of age). Results: No structural changes in the dentin-pulp complex of rats whose mothers were treated with fluoxetine hydrochloride were observed at either dose.Conclusions: Fluoxetine, at the doses administered during pregnancy in this study, did not alter the morphological development of the coronal dentin-pulp complex in their offspring.

Comparison of efficacy and tolerability between sertraline and fluoxetine in patients with major depression

Aim of this study was to compare the efficacy and tolerability between Sertraline and Fluoxetine to determine suitable treatment of major depression in Pakistani population. This study was conducted in the outpatients department of psychiatry, Jinnah Postgraduate depressive disorder were selected. Two groups A1 and A2 were made of 50 patients each. Group A1 received Tab Sertraline while Group A2 received Cap Fluoxetine daily for 24 weeks after going through screening tests and diagnostic evaluation. Efficacy was evaluated by using 21 item Hamilton Depression Rating Scale [HDRS] and 20 item Self Reporting Questionnaire [SRQ]. The patients were asked to attend the OPD every 15 days. Side effects and compliance of the patients was noted at each visit. The results showed that both groups showed significant improvement in depression from week 0 to week 24 with minimal adverse effects. Compliance of the patients in both groups was good. Although HDRS and SRQ scores were significantly reduced in both groups, it was noted that Tab Sertraline improved the symptoms earlier than Cap Fluoxetine. It can be concluded that both sertraline and fluoxetine are efficacious in major depression causing few adverse effects but because sertraline improves symptoms earlier and it is cost effective it may be preferred to fluoxetine

Efecto de la aplicación aguda de fluoxetina sobre una tarea de miedo condicionado al contexto en ratas sometidas a restricción comportamental / Effect of acute Fluoxetine application on a context fear conditioned task in behaviorally restrained rats Laura A

Para estudiar el efecto del aumento comportamental o farmacológico de la ansiedad sobre la adquisición del miedo condicionado al contexto, 32 ratas Wistar (275±25 gm) divididas en dos grupos (restricción comportamental y control) recibieron fluoxetina (ig, 4 mg/kg; 1ml) o solución salina (ig, 0.9%). Luego fueron entrenadas en una tarea de miedo condicionado al contexto. El ANOVA de dos vías mostró diferencias significativas para el factor tratamiento (F[1,28] = 25.261; P < 0.001). Los sujetos tratados con fluoxetina presentaron menor tiempo de congelamiento (Student Newman-Keuls; P < 0.05). No hubo diferencias significativas para la restricción, ni para la interacción entre factores (F[1,28] = 0.115; P = 0.737 y F[1,28] = 0.016; P = 0.899). Así, la restricción no alteró la adquisición del miedo condicionado indicando que el aumento de liberación de 5-HT así inducido, no es comparable al inducido por fluoxetina. La fluoxetina deterioró la adquisición de la respuesta de miedo, indicando que el mecanismo por el cual la ansiedad interrumpe el aprendizaje puede ser serotoninérgico...

In order to study the effect of behavioral or pharmacologically enhanced anxiety on the acquisition of contextual fear conditioning, thirty two Wistar rats (275±25 gm) were divided in two groups (behavioral restriction and control). Half of each group received saline solution (ig.; 0.9%) or fluoxetine (ig.; 4mg/Kg) before the fear conditioning procedure. The two way ANOVA showed significant differences for treatment (F[1,28] = 25.261; P < 0.001). Student Newman-Keuls showed that subjects treated with fluoxetine had lower freezing times. There were no significant differences nor for restriction neither for the interaction between the factors (F[1,28] = 0.115; P = 0.737 y F[1,28] = 0.016; P = 0.899). Thus, the restriction procedure used did not modify the acquisition of the conditioned fear response suggesting that the putative 5-HT enhancement induced is not comparable to that induced by fluoxetine. Acute fluoxetine disrupted the acquisition of the conditioned fear response, suggesting that the mechanism by means of which anxiety disrupts learning could be serotonergic in nature...

Efectividad de la fluoxetina en el tratamiento del síndrome doloroso miofascial / Effectiveness of fluoxetine in the treatment of myofascial pain syndrome

El síndrome doloroso miofascial (SDM) es la causa más frecuente de dolor músculo esquelético persistente presentándose con lumbalgia, cefalea, cervicalgia y dolor escapular. Con una mayor incidencia en mujeres 3:1, siendo su etiología y fisiopatología aún desconocidas. La fluoxetina, un inhibidor selectivo de la recaptación de serotonina, ha demostrado tener efecto analgésico y mejor tolerancia en el dolor tipo crónico. En esta serie de casos prospectiva y multicéntrica, se evaluó la eficacia de la fluoxetina en el tratamiento del SDM. Los pacientes recibieron fluoxetina 20 mg diarios como coadyuvante a su terapia analgésica habitual. El grado de respuesta fue del 97 por ciento en una muestra de 37 pacientes, asociándose a mejoría clínica evidente con reducción del número de analgésicos empleados e intensidad del dolor (p<0.001), evidenciando su efecto analgésico a las 1.5 semanas y antidepresivo a las 2-3 semanas. En conclusión, la fluoxetina es activa en pacientes con SDM, sin efectos adversos y buena tolerancia.

Severa hiponatremia induzida pela associação de fluoxetina, hidroclorotiazida e captopril em paciente jovem / Severe hyponatremia induced by the association of fluoxetine, hydrochlorothiazide and captopril in a young patient

Descrevemos um caso de hiponatremia grave, com um dos níveis séricos de sódio mais baixos da literatura, secundário ao uso de fluoxetina, captopril e hidroclorotiazida. Paciente do sexo feminino, 45 anos, portadora de hipertensão arterial , vinha assintomática em uso de hidroclorotiazida e captopril, quando, há um mês da internação. iniciou-se fluoxetina devido sintomas de depressão. Paciente foi internada por rebaixamento de nível de consciência, com tomografia computadorizada de crânio evidenciando edema cerebral...

We describe a case of severe hyponatremia, with some of the lowest levels of sodium in the literature, secondary to the use of fluoxetine, captropil and hydrochlorothiazide. A 45-year-old female patient suffering from arterial hypertension who was being treated with hydrochlorothiazide and captopril was asymptomatic until one month prior to hospitalization when treatment with fluoxetine was initiated due to depressive symptoms. The patient was hospitalized due to a lower level of consciousness. A CT scan of the skull revealed cerebral edema...

Morphological aspects of the embryonic development of the TMJ in rats (Rattus norvegicus albinus) treated with fluoxetine / Aspectos morfológicos del desarrollo embrionario de la ATM en ratas (Rattus norvegicus albinus) tratadas con fluoxetina

The TMJ has been to the Dental community a key point in the search of knowledge, being it part of the temporomandibular joint complex and of the estomatognathic system which are in charge of the mastication, speech, swallowing, as well as participation in breathing and taste perception. For the majority of the women in serious state of depression, which do not respond psychotherapeutic treatment, pharmacological treatment it's applied. The antidepressants serotonin selective reuptake inhibitors (SSRIs) are the most recommended in these cases. The teratogenic effect of the SSRIs is considered controversial, studies done with women who used these drugs during the pregnancy showed that the respiratory and central nervous systems are the most affected, was also recorded a deficit of body growth and the decrease of the encephalon and skull measures. In the present study, our goal was to assess whether the administration of Fluoxetine during the pregnancy modified the embryology and morphology of the TMJ of rats. For that, 16 Wistar female rats from the Nutrition Department of the UFPE vivarium were selected; 8 for the control group, which received daily 0.9 percent of saline in subcutaneous dose of 10ml/g, with schedules previously established after daily weighing and 8 for the experimental one that were treated with fluoxetine hydrochloride with the dose of 10mg/Kg in a volume 10ml/g of weight, were injected subcutaneously with the same standards established for the control group. It was observed, with this dose that the embryological development of the TMJ, especially of the mandibular condyle, does not present any difference between the degree of maturation of the tissue that forms the TMJ, especially of the condyle between the treated and control groups.

La ATM ha sido para la comunidad odontológica un punto clave en la búsqueda del conocimiento, dado que forma parte del complejo articular temporomandibular y del sistema estomatognático, los cuales se encargan de la masticación, fonación y deglución, así como la participación en la respiración y de la percepción gustativa. Para la mayoría de las mujeres con cuadros graves de depresión, que no responden al tratamiento psicoterapéutico, el tratamiento farmacológico es aplicado. Los antidepresivos del grupo de los Inhibidores Selectivos de Recaptación de Serotonina (ISRSs) son los más comúnmente recomendados en estos casos. El efecto teratogénico de los ISRSs es considerado controversial. Estudios realizados en mujeres que utilizaron estas drogas durante la gestación mostraron que los sistemas respiratorios y nervioso central son los más afectados, también fue constatado un déficit de crecimiento corporal, encefálico y disminución de las medidas craneales. En el presente estudio, nuestro objetivo fue evaluar si la administración de fluoxetina durante la gestación modifica la embriología y la morfología de la ATM de ratas de laboratorio. Para este fin, 16 ratas Wistar del bioterio de nutrición de la UFPE fueron seleccionadas: 8 para el grupo de control, las cuales recibieron diariamente solución fisiológica a 0,9 por ciento en aplicaciones subcutáneas en la dosis de 10ml/g, en horarios previamente establecidos después de pesaje diario y 8 para el experimental, las que fueron tratadas con clorhidrato de fluoxetina en la dosis de 10mg/kg, en un volumen de 10ml/g, inyectados por vía subcutánea en los mismos estándares establecidos para el grupo de control. Se observó, que con esta dosis el desarrollo embriológico de la ATM, especialmente del cóndilo mandibular, no presentó ninguna diferencia entre el grado de maduración de los tejidos que forman la ATM, especialmente del cóndilo, entre los grupos tratado y grupo control.

Fluoxetina: indícios de uso inadequado / Fluoxetine: indication of inadequate use

OBJETIVO: Investigar o uso da fluoxetina na cidade de Santo André, SP, por meio de coleta e análise das receitas especiais (RE) prescritas por médicos e arquivadas nas farmácias e drogarias daquela cidade. MÉTODOS: Foram coletadas as receitas especiais retidas durante os meses de agosto do ano de 2005 a julho de 2006, em 13 farmácias de manipulação e em 27 drogarias em diferentes regiões de Santo André. Cada receita especial foi analisada em relação à presença de fluoxetina, em associação ou não a outros princípios ativos, e o sexo do(a) paciente foi anotado. RESULTADOS: Foram analisadas 39.782 RE - 16.124 coletadas das farmácias magistrais e 23.658 das drogarias. Desses totais, 10.919 prescrições continham fluoxetina - 9.259 provenientes das farmácias magistrais (84,8 por cento) e apenas 1.660 (15,2 por cento) das drogarias. As prescrições de fluoxetina eram predominantemente destinadas a mulheres (79,8 por cento). Na imensa maioria das RE, a fluoxetina foi prescrita em associação com um grande número de outras substâncias ativas, inclusive anfetaminas anoréticas, chegando a mais de dez outras em quase a metade das prescrições. Esse tipo de prescrição múltipla, principalmente para mulheres, é comparado com as prescrições de fórmulas magistrais para emagrecer, muito utilizadas no Brasil. CONCLUSÃO: Os dados obtidos sugerem que a utilização de fluoxetina teria um fim estético (perda de peso), e não um fim terapêutico (tratamento de depressão). Discute-se a relação risco-benefício desse possível uso, que poderia ser classificado de inadequado dado as conhecidas reações adversas da fluoxetina e a sua interferência no sistema citocromo P450.

OBJECTIVE: Investigate the use of fluoxetine in Santo André city, SP, by collecting and analyzing special prescriptions (SP) issued by physicians and filed in compounding pharmacies and drugstores of that city. METHODS: Special prescriptions were collected during August 2005 to July 2006 in 13 compounding pharmacies and 27 drugstores, in different regions of Santo André. Each prescription has been examined for the presence of fluoxetine, in combination or not with other active ingredients, and sex (a) patient was noted. RESULTS: We examined 39,782 SP; 16,124 of them were collected from compounding pharmacies and 23,658 from drugstores. Of these totals, 10,919 prescriptions contained fluoxetine as follows: 9,259 from the compounding pharmacies (84.8 percent) and only 1,660 (15.2 percent) from drugstores. Fluoxetine was manly prescribed for women (79.8 percent). In the vast majority of SP, fluoxetine was prescribed in combination with a large number of other active substances reaching more than ten others in almost half of the prescriptions. CONCLUSION: It is suggested that the large use of fluoxetine possibily aims to an aesthetic objective (to lose weight) and not as a therapeutic aim (treatment of depression). This work discusses the risk/benefit of this use which could be described as inappropriate, given the known adverse reactions of fluoxetine and its interference with the cytochrome P450 system.

[Comparison of the effect of Fluoxetine and Imipramine on fasting blood sugar of patients with major depressive disorders, four and eight weeks after treatment]

Depression is one of the most ancient and prevalent mood disorders in psychiatry. Risk of depression is 10-25% in women and 5-12% in men. since diabetes mellitus and its complications can lead to depression and vice versa, control of blood glucose levels in patients with depression and knowledge of the effect of antidepressant drugs on blood glucose levels are important. This study was performed to determine the effect of Fluoxetine and Imipramine on the fasting blood sugar [FBS] of patient with major depressive disorders. This study was a parallel randomized clinical trial based on diagnostic criteria of DSM-IV-TR. The subjects were selected randomly from the patients referring to Shahid Hashemi Senejani Hospital of Arak and private office. The patients were assigned into two groups; each group consisted of 40 subjects. Group A received fluoxetine 20 mg/day and group B received imipramine 100 mg/day. Measurement of FBS was performed before treatment, four weeks and eight weeks after treatment. Data were analyzed by means of descriptive statistics, KS [Kolmogorov-Smirnov test] and paired t-test. There were no significant statistical differences between first and second times mean FBS values in groups A and B, but there were significant statistical differences in the third time mean GBS values between the two groups [P=0.001]. Also there was not any significant difference in the first and second time mean FBS values in group A [P=0.424] too. A significant decrease in the first and third time mean FBS values was noticed [P=0.039]. There was also a significant increase in the second and third times mean FBS values compared with the first time mean FBS values in group B [P<0.05]. This study revealed a decrease in FBS mean values after 8 weeks of treatment with Fluoxetine and an increase in FBS after 4 and 8 weeks of treatment with Imipramine. Therefore, we recommend Fluoxetine for treatment of depression in the patients with hyperglycemia, and Imipramine for depression in the patients with hypoglycemia

Pontine and extrapontine osmotic myelinolysis after the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

Osmotic demyelination syndrome (ODS) may be precipitated by aggressive correction of a hypo or hyper-osmolar states. We describe the case of a 53-year-old woman that was started on fluoxetine 20 mg/day for depression and nine days later was found to have fluoxetine-induced syndrome of inappropriate secretion of antidiuretic hormone. After hyponatremia correction the mental status of the patient gradually improved, but subsequently she had intermittent difficulty in speaking, naming objects, memory deficits and psychomotor slowness. Magnetic resonance revealed bilateral symmetric hyperintense lesions in the basal ganglia, temporal lobe and hippocampal formation compatible with ODS. These symptoms gradually resolved and she was discharged home without any deficits. Two months later, a new image showed lesion in pons and the other lesions had disappeared. Fluoxetine therapy had never been related with a complication like that.

A síndrome de desmielinização osmótica (SDO) pode ser precipitada pela correção agressiva de um estado hiper ou hipoosmolar. Nós descrevemos o caso de mulher de 53 anos que havia iniciado o uso de fluoxetina 20 mg/dia para depressão e que nove dias depois foi diagnosticada como tendo síndrome da secreção inapropriada de hormônio antidiurético induzida por fluoxetina. Depois da correção da hiponatremia o estado mental da paciente gradualmente melhorou, mas subsequentemente ela apresentou dificuldade intermitente para fala e para nomear objetos, déficits de memória recente e lentidão psicomotora. Ressonância magnética revelou lesões hiperintensas bilaterais e simétricas na região dos gânglios da base, lobo temporal e hipocampo compatíveis com SDO. Estes sintomas gradualmente se resolveram e a paciente foi de alta sem qualquer déficit. Dois meses mais tarde uma nova imagem cerebral mostrou lesão na ponte e ausência das lesões antigas. Até onde sabemos a terapia com fluoxetina nunca foi relacionada a uma complicação tardia como esta.

Tolerability and effectiveness of fluoxetine, metformin and sibutramine in reducing anthropometric and metabolic parameters in obese patients / Tolerabilidade e eficácia da fluoxetina, metformina e sibutramina na redução de parâmetros antropométricos e metabólicos em pacientes obesos

The aim of this study is to assess the effects of sibutramine (S) 15 mg/day, fluoxetine (F) 60 mg/day, and metformin (M) 1,700 mg/day, as an adjunct therapy to a 1,500 kcal/day diet, in reducing anthropometric and metabolic parameters. S (n= 8), F (n= 9), and M (n= 8) were compared to placebo (n= 10) in 35 obese patients in a 90-day trial. Side effects were also studied during the treatment. The data demonstrated that F therapy resulted in a greater average reduction in BMI (11.0 percent), weight (10.0 percent), abdominal circumference (11.0 percent) and percentfatty-tissue (12.8). An elevation in HDL-cholesterol (25.8 percent) and a reduction in average triglyceride levels (28.3 percent) were also shown. S presented a 7.91 percent reduction in the abdominal circumference and a 9.65 reduction in percentfatty-tissue was also found. M group presented reductions in BMI (4.03 percent), waist circumference (6.92 percent), HOMA (23.5 percent) and blood pressure (6.08 percent in systolic and 2.08 percent in diastolic). In general, the three drugs can be considered well tolerated. We concluded that F and S demonstrated a greater mean reduction in anthropometric and metabolic parameters when compared to M, however all of them are useful for that purpose, when the subjectsÆ characteristics are considered.

O objetivo deste estudo foi avaliar o efeito da sibutramina (S) 15 mg/dia, fluoxetina (F) 60 mg/dia, e metformina (M) 1.700 mg/dia, associadas a uma dieta de 1.500 kcal/dia, na redução de parâmetros antropométricos e metabólicos. S (n= 8), F (n= 9) e M (n= 8) foram comparadas ao placebo (n= 10) em 35 pacientes obesos durante 90 dias de tratamento. As reações adversas também foram avaliadas durante o tratamento. O grupo F demonstrou uma redução no IMC (11,0 por cento), peso (10,0 por cento), circunferência abdominal (11,0 por cento) e por cento de tecido adiposo (12,8). Também foram observados um aumento nos níveis de HDL-colesterol (25,8 por cento) e uma redução nos níveis de triglicérides (28,3 por cento), no grupo F. O grupo S apresentou uma redução de 7,91 por cento na circunferência abdominal e de 9,65 na por cento de tecido adiposo. Já o grupo M apresentou reduções no IMC (4,03 por cento), circunferência abdominal (6,92 por cento), HOMA (23,5 por cento) e pressão arterial (6,08 por cento na sistólica, 2,08 por cento na diastólica). Os três fármacos analisados foram bem tolerados durante o tratamento. Concluímos que a F e a S demonstraram maior eficácia na redução dos parâmetros antropométricos e metabólicos dos pacientes obesos quando comparadas à M, entretanto todas podem ser prescritas para essa finalidade, desde que sejam consideradas as características individuais dos pacientes.

Severe hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

A hiponatremia é complicação significativa do tratamento com inibidores seletivos da recaptação da serotonina (ISRS). Descrevemos o caso de uma paciente de 53 anos de idade que iniciou uso de fluoxetina 20 mg/dia para depressão. Nove dias depois, a paciente apresentou fraqueza, náusea, progredindo para confusão, inapetência e vômitos. Três horas depois ela tornou-se irresponsiva e teve uma crise convulsiva generalizada. Foi então trazida ao nosso serviço de emergência. Na admissão, a paciente estava normovolêmica, sem déficits motores focais, mas apresentava leve rigidez muscular generalizada e sinal de Babinski bilateralmente. O sódio sérico era 105 mmol/L, osmolaridade sérica, 220 mmol/L, e osmolaridade urinária, 400 mmol/L. Os outros exames laboratoriais, Raio-X do pulmão, líquido cefalorraqueano e tomografia do crânio eram normais. Ela foi diagnosticada como tendo SSIHAD induzida por fluoxetina sendo esta descontinuada. Nós iniciamos a correção da hiponatremia e, em 5 dias, o estado mental da paciente gradualmente retornou ao normal, paralelamente a resolução da hiponatremia. SSIHAD e hiponatremia devem ser consideradas em um paciente que apresenta deterioração de sua condição clinica quando estiver em uso de ISRS. O uso de antidepressivos ISRS deve ser lembrado no diagnóstico diferencial de hiponatremia induzida por drogas.

Fluoxetine withdrawal syndrome in the newborn.

A term baby was admitted to our neonatal unit with jitteriness, hypertonia, sneezing and fever. Her mother was on 20 mg of fluoxetine throughout her pregnancy. These symptoms which were possibly due to fluoxetine withdrawal lasted only for a short while. We attempt to look at the reported prevalence of this condition in the literature.